An Efficacy, Safety and Pharmacokinetic Study on the Short-term and Long-term Use of Metformin in Obese Children and Adolescents
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 2
- 主要终点
- Change in BMI from baseline
研究概览
简要总结
The purpose of this study is to determine whether metformin is effective in reducing BMI and insulin resistance in obese children and adolescents.
详细描述
The prevalence of obesity in children and adolescents is increasing rapidly and is associated with significant medical and psychosocial consequences persisting into adulthood.
Obesity may lead to metabolic complications, such as insulin resistance, which can progress via impaired fasted glucose and impaired glucose tolerance to type 2 diabetes mellitus (T2DM) and to the development of micro- and macro-vascular complications.
Metformin, an oral anti-diabetic licensed for T2DM for adults and children from 10 years onwards, is already used off label in obese children and adolescents with insulin resistance, even though the specific effects of metformin in these obese children and adolescents have not been elucidated, particularly upon long-term use.
The rationale for this study is based on the hypothesis that metformin may reduce body mass index (BMI), insulin resistance and percentage of body-fat in obese children and adolescents with insulin resistance. Further more it is anticipated that metformin may delay the progression to T2DM and thereby micro- and macro-vascular complications in obese children and adolescents with insulin resistance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 10 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 10 and ≤ 16 years at study entry
- •Caucasian descent
- •Obesity defined as BMI-SDS > 2.3
- •Insulin resistance defined as HOMA-IR ≥ 3.
- •An obtained informed consent from subjects and parents/caregivers.
排除标准
- •Presence of T2DM (American Diabetes Association criteria)
- •Presence of endocrine disorders with steroid therapy
- •Suspicion of polycystic ovarium syndrome;
- •Height < -1.3 SD of target height;
- •Syndrome disorders with or without mental retardation;
- •Use of anti-hyperglycaemic drugs;
- •Pregnancy (pregnancy test will be performed, if applicable);
- •(History of) alcohol abuse;
- •Impaired renal and/or hepatic function (defined as GFR < 80 ml/min. GFR=40 x length (cm) / serumcreatinin (μmol/l and ALAT >150% of normal value for age);
- •Use of ritonavir; use of ACE inhibitors;
- •Insufficient knowledge of the Dutch language.
研究组 & 干预措施
Metformin
Metformin with lifestyle intervention during 18 months
干预措施: Metformin (Drug)
Metformin
Metformin with lifestyle intervention during 18 months
干预措施: Lifestyle intervention (Behavioral)
Placebo
Placebo and lifestyle intervention during 18 months
干预措施: Lifestyle intervention (Behavioral)
结局指标
主要结局
Change in BMI from baseline
时间窗: 18 months and 36 months
Change in BMI after part 1 (double blind) and part 2 ( follow-up)
Change in Insulin resistance from baseline
时间窗: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months
calculated by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR).
次要结局
- Renal and hepatic function(3; 6; 9; 12; 15; 18; 24; 30 and 36 months)
- Tolerability(3; 6; 9; 12; 15; 18; 24; 30 and 36 months)
- Long term efficacy(36 months)
- Long-term safety(36 months)
- Microvascular complications(36 months)
- Macrovascular complications(36 monthts)
- Development of T2DM(36 months)
- PK-parameters: volume of distribution (liters)(9 months)
- Pharmacokinetics (PK)-parameters: clearance (ml/min)(9 months)
- Body fat percentage(0, 9, 18 and 36 months)
- Physical fitness(0, 9, 18 and 36 months)
- Quality of life(0, 9, 18 and 36 months)
- Long-term tolerability(36 months)
研究者
Van der Vorst
Mrs. M.M.J. van der Vorst, paediatrician-clinical pharmacologist
St. Antonius Hospital